Vinyl choloroformate (VOC-C1) has been introduced by this laboratory as a highly effective reagent for the protection of amino and hydroxyl groups and for the selective N-dealkylation of tertiary amines. Efficient syntheses of naloxone and nalbuphine proposed research is the further development of the VOC moiety as a preparative tool, particularly in the area of peptide syntheses. To reach this goal, new reagents for the transfer of substituted enyloxycarbonyl species to nucleophiles are required along with general methodology for the formation of substituted enol derivatives including enol carbamates, carbonates, and haloformates. Recent advances include the first general route to enol chloroformates, two useful new syntheses of enol carbamates and carbonates including a catalytic process which is both regiospecific and stereospecific, an efficient preparation of fluoroformates, and three new active acylating systems for the transfer of enyloxycarbonyl moieties to amino acids. Other goals in peptide chemistry include the design and development of better reagents for "racemization free" peptide bond formation based on the reactions of "hot" reagents with peptide acids to directly produce under mild conditions "cool", weakly activated peptide ester acylating agents. Other methodology developed under this grant includes new routes to isoxazoles and other synthetically and pharmaceutically useful heteroaromatic systems. X-ray crystal structure proofs have been supplied for some products. Reagents and processes for other synthetically useful transformations also are under study.